Androgen deficiency and erectile dysfunction (ED) are 2 common, but independently distributed, disorders that co-exist in a significant proportion of men with ED. The role of androgen deficiency in the pathophysiology of sexual dysfunction in men with ED remains misunderstood. The primary objective of this study is to determine whether testosterone replacement in men with low testosterone levels who present with ED improves therapeutic response to sildenafil citrate by improving erectile function, stimulating sexual desire, improving partner intimacy, affectivity balance, and sense of well being, and augmenting penile rigidity. We will conduct a double-blind, placebo-controlled, parallel-group, randomized clinical trial in men, 40-70 years of age, who present with mild to moderate ED and have androgen deficiency defined as total testosterone levels (measured by liquid chromatography tandem mass spectrometry, LC-MS/MS) below 300 ng/dL and/or free testosterone levels by equilibrium dialysis below 50 pg/ml. During the 6-week control period, the eligible men will initially take 50 mg sildenafil citrate, as often as necessary, but no more than once daily for 3-weeks or 8 doses, whichever is greater;at which point the dose will be increased to 100-mg in those not responding to 50-mg dose. After an additional 3-weeks on a stable, optimized, dose of sildenafil citrate, men would be randomized to receive the optimized dose of sildenafil citrate plus placebo gel or sildenafil citrate plus a replacement dose (100 mg daily) of testosterone gel. The dose of testosterone gel (100 mg) was selected to increase testosterone concentrations into the mid-normal range for young men (approx. 650-700 ng/dL). Erectile function assessed by IIEF, sexual encounter profile (subject and partner), global efficacy assessment, impact of ED on quality of life by ED Impact scale and Life Satisfaction Survey, overall sexual activity, sexual desire by MSHQ and sexual desire domain of IIEF, partner interaction and intimacy, affectivity balance by DeRogatis Affectivity Balance Scale, penile rigidity in response to a visual erotic stimulus after sildenafil citrate administration would be evaluated at baseline, and after 12-weeks of treatment. Careful attention to subject selection, potential confounders, effect size and power considerations, state-of-the-art methods, randomized, placebo-controlled study design, and a multi-disciplinary team of investigators would help elucidate the effects of testosterone in men with ED. The proposed study would provide a rational basis for testosterone administration in a significant subset of men with erectile dysfunction, and also provide an excellent opportunity for making further gains in our understanding of the role of testosterone in the regulation of sexual function in men.